In the GCP inspections conducted in 2011, it was observed that Investigational Product (IP) management contributed to 33.3% of the critical GCP Inspection Findings and 40% of the major GCP Inspection Findings in 2011 respectively. Of these findings, 55.5% was related to IP re-packaging process. This was observed when local sites had to perform the randomization and blinding procedures specifically repacking the IP and comparator product for each subject according to the randomisation code.
This guideline summarizes the salient points to be considered when re-packaging Investigational Products.
The goals of IP management include the following:
• | Ensure protection and safety of trial subjects, so that they are not placed under unnecessary risk |
• | Ensure traceability of the investigational product |
• | Ensure accuracy clinical trial data, that it is unaffected by inadequate safety, quality or efficacy arising from unsatisfactory manufacture, handling and storage of the investigational product |
• | Ensure that there is consistency between batches of the same investigational product used in the same or different clinical trials |
Roles and Responsibilities
It is critical to delineate the roles and responsibilities of blinded and unblinded study staff involved in IP management so as not to compromise the study blind for blinded clinical trials. Unblinded study staff should be involved in IP management concerning IP shipment, receipt, storage of the bulk IP, re-packaging and destruction, whilst blinded study staff should be involved in IP Storage of the re-packaged IP, Dispensing, Accountability, and Return. It is the Principal Investigator's responsibility to ensure that these roles and responsibilities are adequately documented on the Signed Signature Sheet.
The following flowchart summarizes the responsibilities of the unblinded and blinded study staff in IP management and the required documentation to be maintained.
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Good Manufacturing Practice (GMP) Principles of IP Re-Packaging
IP Re-packaging may be performed outside of a GMP-certified facility. However, the principles of GMP should be adhered to, where applicable.
Sections 23 to 25 PICS Annex 13 provide guidance on IP re-packaging:
• | Line clearance: Pack one type of Investigational Product at a time. |
• | In-process control checks: IP re-packaging should be performed and witnessed by delegated and trained unblinded study staff. |
• | Label re-conciliation : No. of IP labels issued = No. of IP labels used + destroyed + remaining; The Sample IP Label must comply with Medicines (Clinical Trials) Regulation 18 and SGGCP 4.6.3 |
• | Documentation: The IP re-packaging process should be documented and signed off by the unblinded study staff. It would be recommended to affix the sample IP label(s) onto this documentation for reference purposes. |
Standard Operating Procedures (SOPs) for IP Management
It would the Sponsor's responsibility to develop written instructions for handling and storage the IP i.e. IP shipment, IP receipt, IP storage, IP re-packaging, IP dispensing and accountability, IP Return and / or Destruction, and unblinding procedures (Ref: SGGCP 5.14.3).
The template forms for IP Management attached in this guidance may be customized in accordance to your protocol.
Maintainence of IP Documentation
The unblinded study staff should maintain the following IP Documentation in a separate Pharmacy Binder on site with limited and secure access:
• | Master Randomization List |
• | Separate IP Inventory Logs for the active and placebo IP |
• | IP Storage Temperature Logs for the bulk IP |
• | IP Relabelling and Re-packaging Form |
• | IP Destruction Form |
The blinded study staff should maintain the following IP Documentation in the Investigator Site Files:
IP Dispensing and Accountability Logs
Useful References
Medicines (Clinical Trials) Regulations
Singapore Guideline for Good Clinical Practice
PICS Annex 13
Template Forms for IP Management
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